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Intracranial haemorrhage (ICH) is a rare but devastating complication post spinal surgery. We present three cases of post spine surgery ICH that were associated with high drain outputs postoperatively. The first patient underwent C1–C6 instrumented fusion and C4–C6 decompression. 950 mls hemoserous fluid was drained via suction drain immediately postoperatively. He suffered cerebral hemorrhage with tonsillar herniation and was brain dead on the same night. The second patient underwent C1–T1 instrumented fusion with C3–C4 decompression. 400 mls hemoserous fluid was drained via suction drain shortly after skin closure. He suffered subdural hemorrhage, subarachnoid hemorrhage and intraventricular hemorrhage, with persistent neurologic deficits and required long-term institutionalised care. The third patient underwent L2–L4 decompression and instrumented fusion. 480 mls hemoserous fluid was drained via suction drain 2 hours postoperatively. He suffered subdural haemorrhage but eventually recovered fully. An excessive drain output, especially within first few minutes to hours postoperatively, may signify a CSFleak. Suction drains should be used with caution in these cases as negative suction in the presence of a dura tear increases risk of post spine surgery ICH. In these cases, the use of non-suction drains should be considered. [ABSTRACT FROM AUTHOR]

The vagal, stellate, and cardiac ganglia cells changes following subarachnoid hemorrhage (SAH) may occur. This study aimed to investigate if there is any relation between vagal network/stellate ganglion and intrinsic cardiac ganglia insult following SAH. Twenty-six rabbits were used in this study. Animals were randomly divided as control (GI, n = 5); SHAM 0.75 cc of saline-injected (n = 5) and study with autologous 1.5 cc blood injection into their cisterna magna(GIII, n = 15). All animals were followed for three weeks and then decapitated. Their motor vagal nucleus, nodose, stellate, and intracardiac ganglion cells were estimated by stereological methods and compared statistically. Numerical documents of heart-respiratory rates, vagal nerve- ICG, and stellate neuron densities as follows: 276 ± 32/min-22 ± 3/min-10.643 ± 1.129/mm3-4 ± 1/mm3-12 ± 3/mm3 and 2 ± 1/cm3 in the control group; 221 ± 22/min-16 ± 4/min-8.699 ± 976/mm3-24 ± 9/mm3-103 ± 32/mm3 and 11 ± 3/cm3 in the SHAM group; and 191 ± 23/min-17 ± 4/min-9.719 ± 932/mm3-124 ± 31/mm3-1.542 ± 162/mm3 and 32 ± 9/cm3 in the SAH (study) group. The animals with burned neuro-cardiac web had more neurons of stellate ganglia and a less normal neuron density of nodose ganglia (p < 0.005). Sypathico-parasympathetic imbalance induced vagal nerve-ICG disruption following SAH could be named as Burned Neurocardiac Web syndrome in contrast to broken heart because ICG/parasympathetic network degeneration could not be detected in classic broken heart syndrome. It was noted that cardiac ganglion degeneration is more prominent in animals' severe degenerated neuron density of nodose ganglia. We concluded that the cardiac ganglia network knitted with vagal-sympathetic-somatosensitive fibers has an important in heart function following SAH. The neurodegeneration of the cardiac may occur in SAH, and cause sudden death. Graphical abstract [ABSTRACT FROM AUTHOR]

Objective: To investigate the prognostic value of inflammatory markers, including neutrophil/lymphocyte ratio (NLR), derived neutrophil/lymphocyte ratio (dNLR), platelet/lymphocyte ratio (PLR), monocyte/ lymphocyte ratio (MLR), prognostic nutritional index (PNI), and systemic inflammation response index (SIRI) in patients with aneurismal subarachnoid hemorrhage (aSAH), and then develop a Nomogram prognostic model. Methods: We analysed 178 aSAH patients who underwent surgery at Subei People's Hospital of Jiangsu province from January 2015 to December 2017. Patients were divided into two groups according to Glasgow outcome scale (GOS) score at 3 months. Univariate and multivariate analysis were used to identify the association between inflammatory markers and prognosis. Subsequently, we identified the best cutoff of SIRI for unfavorable outcome using receiver operating characteristic (ROC) curve analysis and compared the clinical data between high and low SIRI levels. We further evaluated the additive value of SIRI by comparing prognostic nomogram models with and without it. Results: A total of 47 (26.4%) patients had a poor outcome. Multivariate logistic regression analysis showed that SIRI was an independent risk factor of poor outcome. The SIRI of 4.105 x 109/L was identified as the optimal cutoff value, patients with high SIRI levels had worse clinical status and higher rates of unfavorable outcome. ROC analysis showed that a nomogram model combining the SIRI and other conventional factors showed more favorable predictive ability than the model without the SIRI. Conclusions: SIRI was independently correlated with unfavorable outcome in SAH patients, and the nomogram model combining the SIRI had more favorable discrimination ability. [ABSTRACT FROM AUTHOR]

Endoscopic resection can be used for removing colloid cysts as a substitute for open craniotomy. Cerebral vasospasm, a possible complication of the craniotomy procedure, has not been reported as a complication of endoscopic removal of colloid cysts. A 58-year-old man developed the worst headache of his life. The CT and MRI showed a 1.3 cm midline third ventricular cyst at the level of the foramen of Monro, consistent with a colloid cyst. The patient elected to undergo an endoscopic resection of the colloid cyst. The image-guided frameless stereotactic endoscopic colloid cyst resection proceeded without events. Postoperative MRI showed a gross total resection. The patient continued to improve until post-operative day #9 when he experienced an episode of slurred speech and several episodes of legs buckling. An MRI did not show a stroke. A CT angiogram showed diffuse vasospasm, including the basilar artery and bilateral middle cerebral arteries, when compared to the patient's preoperative MRA. The patient's antihypertensive medications were stopped. The patient was started on Nimodipine, 60 mg every 4 hours, and triple H therapy (Hypertension, Hypervolemia, and Hemodilution) was applied. His blood pressure rose and his neurologic exam improved over several days. The patient returned to his baseline in 14 days without any neurological deficits. To our knowledge, this is the first case report of a patient undergoing endoscopic colloid cyst resection that was complicated by diffuse cerebral vasospasm. We report the first case of acute, transient cerebral vasospasm following endoscopic resection of a colloid cyst. [ABSTRACT FROM AUTHOR]

A 42-year-old lady presented with acute aneurysmal subarachnoid haemorrhage and developed difficulty recognising faces (prosopagnosia), inability to process visual information in busy environments (simultagnosia) and difficulty to read (alexia). She was subsequently found to have superficial siderosis on MRI. [ABSTRACT FROM AUTHOR]

Recently, the diverse functions of microRNAs (miRNAs) in brain diseases have been demonstrated. We intended to uncover the functional role of microRNA-130b (miR-130b) in cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH). SAH was induced by injecting the autologous blood into the cisterna magna of Sprague Dawley rats. The cerebral vascular smooth muscle cells (cVSMCs) were extracted for in vitro experimentation. In vitro and in vivo assays were implemented with transfection of miR-130b mimic/inhibitor, sh-Kruppel-like factor 4 (KLF4), oe-KLF4 plasmids or p38/MAPK signaling pathway agonist (anisomycin), respectively, to elaborate the role of miR-130b in CVS following SAH. Elevated miR-130b and reduced KLF4 were found in SAH patients and rat models of SAH. KLF4 was the target gene of miR-130b. miR-130b promoted the proliferation and migration of cVSMCs through the Inhibition of KLF4. Besides, KLF4 inhibited the proliferation and migration of cVSMCs through blockage of the p38/MAPK pathway. Furthermore, in vivo assay confirmed the inhibitory effect of decreased miR-130b in CVS following SAH. In conclusion, miR-130b may activate the p38/MAPK signaling pathway through targeted inhibition of KLF4, thereby contributing to some extent to the development of cerebral vasospasm after SAH. [ABSTRACT FROM AUTHOR]

Spontaneous intracranial hypotension (SIH) combined with subarachnoid hemorrhage (SAH) has rarely been reported. Herein, we report two patients with SIH who suffered from diffuse non-aneurysmal SAH and expanded the symptom spectrum of SIH. (1) A 55-year-old male was diagnosed with SIH based on orthostatic headache and diffuse pachymeningeal enhancement on brain MRI. One more month later, his headache was exacerbated, and brain CT showed diffuse SAH. Lumber puncture showed bloody cerebrospinal fluid (CSF) with a low CSF pressure of 20 mmH2O after a 30 mL intrathecal injection of saline. The patient was treated with a lumbar epidural blood patch and recovered. (2) A 41-year-old male presented with orthostatic headache and nuchal pain. The brain CT scan confirmed the diagnosis of SAH. Brain MRI revealed diffuse dural thickening and bilateral frontoparietal subdural fluid collection. Lumber puncture showed bloody CSF with low CSF pressure. Then, an epidural blood patch was performed with satisfactory results. Dilation and rupture of intracranial venous structures might play significant roles in SIH combined with SAH. We should be alert to SIH patients who develop a new persistent severe headache without relief after lying down or a suddenly changed state of consciousness. [ABSTRACT FROM AUTHOR]

Patients who have experienced an aneurysmal subarachnoid hemorrhage (aSAH) may face a significant morbidity burden following the acute phase of their injury. Though commonly employed as an anticoagulant, heparin may have clinical utility related to its ability to mitigate the production of pro-inflammatory cytokines and chelate oxidized blood. A comprehensive review of the literature was conducted on PubMed, MEDLINE, Scopus, Cumulative Index of Nursing and Allied Health Library and Web of Science with the assistance of a medical reference librarian from January 2018 to March 2022. Two pieces of literature were evaluated in this review, both of which sought to determine the either efficacy or safety of heparin infusions in patients following an aSAH. The small sample size and the heterogeneity of outcome data reported makes defining a role in therapy for heparin difficult; however, it may be reasonable to use lower weight-based doses and to target a lower aPTT goal when considering a heparin infusion in these patients. Many options beyond heparin infusions exist in the armamentarium for clinicians when managing aSAH patients. Additional research is required to elucidate therapeutic drug monitoring targets and dosing protocols. [ABSTRACT FROM AUTHOR]

We report a unique case of late-onsetcerebral vasospasm at 21 and again at 30 days following aneurismal subarachnoid hemorrhage. [ABSTRACT FROM AUTHOR]

Aneurysmal Subarachnoid haemorrhage (aSAH) is one of the most common causes of neurocritical care admission. Consistent evidence has been suggestive of endocrine dysregulation in aSAH. This review aims to provide an up-to-date presentation of the available evidence regarding endocrine dysregulation in aneurysmal subarachnoid haemorrhage. A comprehensive literature search was performed using PubMed database. All available evidence related to endocrine dysregulation in hypothalamic-pituitary hormones, adrenal hormones and natriuretic peptides after aSAH, published since 2010, were reviewed. There have been reports of varying prevalence of dysregulation in hypothalamic-pituitary and adrenal hormones in aSAH. The cause of this dysregulation and its pattern remain unclear. Hypothalamic-pituitary and adrenal dysregulation have been associated with higher incidence of poor neurological outcome and increased mortality. Whilst there is evidence that long-term dysregulation of these axes may also develop, it appears to be less frequent than the acute-phase dysregulation and transient in pattern. Increased levels of catecholamines have been reported in the hyper-acute phase of aSAH with reported inconsistent correlation with the outcomes and the complications of the disease. There is growing evidence that of a causal link between the endocrine dysregulation and the development of hyponatraemia and delayed cerebral ischaemia, in the acute phase of aSAH. However, the pathophysiological mechanism and pattern of endocrine dysregulation which could be causally associated with these complications still remain debatable. The evidence, mainly from small observational and heterogeneous in methodology studies, is suggestive of adverse effects of the endocrine dysregulation on the outcome and the incidence of complications of the disease. However, the cause of this dysregulation and a pathophysiological mechanism that could link its presence with the development of acute complications and the outcome of the aSAH remain unclear. Further research is warranted to elucidate the clinical significance of endocrine dysregulation in subarachnoid haemorrhage. [ABSTRACT FROM AUTHOR]

Endovascular techniques are becoming more common for cerebral aneurysms, but not all patients are suitable and open surgery is necessary for some. The traditional pterional approach requires a large craniotomy and this carries some morbidity in itself. With the growing expectation for minimally invasive surgery, we present our experience in supraorbital mini-craniotomy for good grade aneurysmal subarachnoid haemorrhage. Data on good-grade subarachnoid haemorrhage patients having aneurysms clipped via this approach were collected prospectively. Aneurysms at all anterior circulation sites were included, with the exception of the pericallosal artery, which was not within reach. A long-term follow-up questionnaire was sent to patients who had a supraorbital approach to clip the aneurysm at more than 1 year from hospital discharge. Our results demonstrate mortality of 1% and severe residual disability in 10% of patients. Approach-related complications were low and it was considered that the operating space was not restricted in any of our cases. Return to work was achieved in 70% of patients who were working at the time of their haemorrhage. Supraorbital micro-craniotomy is a safe approach for patients with proximal anterior circulation aneurysms, with low mortality and morbidity. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether the Serum Netrin-1 and Urinary KIM-1 (Kidney Injury Molecule-1) levels are associated with the detection of preeclampsia. A total of 90 patients, including 36 normal pregnant women, 29 patients with nonsevere preeclampsia and 25 patients with severe preeclampsia, were included in this study. Maternal serum Netrin-1 and Urinary KIM-1 levels were measured by using an enzyme-linked immunosorbent assay (ELISA). The results showed that the Levels of Netrin-1 and KIM-1 were statistically higher in women with preeclampsia as compared with normal pregnant women. Furthermore, the Netrin-1 level in women with severe preeclampsia was significantly higher than nonsevere preeclamptic women. inconclusion the current study showed that Maternal serum level of Netrin-1 and Urinary level of KIM-1 can be used as early biomarkers for the detection of preeclampsia. What is already known on this subject? Preeclampsia is a disorder of widespread vascular endothelial malfunction and vasospasm that occurs after 20 weeks' gestation. Netrin-1 was found to promote angiogenesis. Alteration of placental angiogenesis in early pregnancy is a well-known reason for placental dysfunction such as preeclampsia. Kidney injury with proteinuria is a characteristic feature of preeclampsia. Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. Due to these facts, we aimed to investigate the role of maternal serum Netrin-1 and Urine KIM-1 levels in preeclampsia presence and severity. What the results of this study add? A significant relationship between Netrin-1 and KIM-1 levels with preeclampsia. What the implications are of these findings for clinical practice and/or further research? Based on these findings, we concluded that increased levels of Netrin-1 and KIM-1 are associated with severe preeclampsia. [ABSTRACT FROM AUTHOR]

A clinical hallmark of aneurysmal SAH (aSAH) is headache. Little is known about post-aSAH headache factors which may point to underlying mechanisms. In this study, we aimed to characterize the severity and trajectory of headaches in relation to clinical features of patients with aSAH. This is a retrospective longitudinal study of adult patients admitted to an academic tertiary care center between 2012 and 2019 with aSAH who could verbalize pain scores. Factors recorded included demographics, aneurysm characteristics, analgesia, daily morning serum sodium concentration, and occurrence of vasospasm. Group-based trajectory modeling was used to identify headache pain trajectories, and clinical factors were compared between trajectories. Of 91 patients included in the analysis, mean age was 57 years and 20 (22%) were male. Headache score trajectories clustered into two groups: patients with mild-moderate and moderate-severe pain. Patients in the moderate-severe pain group were younger (P<0.05), received more opioid analgesia (P<0.001), and had lower sodium concentrations (P<0.001) than patients in the mild-moderate pain group. We identified two distinct post-aSAH headache pain trajectory cohorts and identified an association with age, analgesia, and sodium levels. Future prospective studies considering sodium homeostasis and volume status under standardized analgesic regimens are warranted. [ABSTRACT FROM AUTHOR]

With the prolongation of the onset time after the rupture of highly distinct intracranial aneurysms, serious complications such as re-rupture hemorrhage, cerebral vasospasm and hydrocephalus often occur, which may lead to the death of the patient. Based on the above background, the purpose of this study is to analyze the curative effect of super early clipping for ruptured intracranial aneurysms with high grade. This paper mainly introduces the operation points and techniques of the pterional approach and the supracrubral lateral orbital approach, and then collects the clinical data of patients with intracranial ruptured aneurysm treated by craniotomy clip-clip-on in shenbei New District Central Hospital from June 2015 to July 2018. The results show that the supraorbital lateral approach is a minimally invasive, relatively safe approach with satisfactory field exposure. The superior lateral orbital approach is suitable for the treatment of high grade intracranial ruptured aneurysms as well as anterior circulation aneurysms. Compared with the pterional approach, it has the advantages of avoiding the injury of facial nerve branch, short operation time, small operation trauma, short average length of hospital stay, fewer complications, quick postoperative recovery and so on. [ABSTRACT FROM AUTHOR]

With a median of 5.5 (IQR 4-6, range 4-8) treatments including the anti-PD-1, the most used second line treatment was ESHAP in 12 patients (40%). Hodgkin lymphoma (HL) is a good-prognosis malignancy, with an 80% 5-year progression-free survival (PFS) in patients between 18 and 64 years old [[1]]. Our group previously showed a 43% two-year overall survival (OS), 27% two-year PFS and 46% of relapses in a cohort of 113 patients with r/r HL with only 2% treated with anti-PD1 before allo-SCT. [Extracted from the article]

Intracranial aneurysms are acquired lesions resulting from hemodynamic stress on the vascular wall. Their rupture usually presents as a subarachnoid hemorrhage (SAH) with a high mortality rate. Cerebral vasospasm follows, which leads in many cases to delayed brain ischemia and even death. We aimed to explore the relationship between cerebral perfusion and coronavirus disease (COVID-19) in aneurysmal SAH. We analyzed 42 cases that underwent treatment for proven SAH due to ruptured cerebral aneurysms between January 2020 and December 2021. The patients were treated adhering to a standard protocol. The cerebral vasospasm was assessed by measuring the difference in the mean arterial pressure of the carotid artery relative to the internal cerebral artery (Lindegaard's ratio) by transcranial Doppler ultrasound for 12 consecutive days. Twenty-three patients showed no signs of an acute respiratory syndrome associated with COVID-19 but tested positive for the SARS-coronavirus 2 (SARS-CoV-2). The control group included 19 SARS-CoV-2 negative cases. The mean age was 59.7 ± 8.4 years (range 44-72), with 29 males and 13 females. The mean arterial pressure was without a significant difference of 89.3 ± 3.3 to 89.7 ± 3.7 mmHg in SARS-CoV-2 negative to positive patients. When viral infection was evident, we observed a higher Lindegaard's ratio of 2.12 ± 0.36 than the control, with a value of 1.43 ± 0.33 (p < 0.01). Thus, brain perfusion was 32.5% better in negative patients. We suggest that SARS-CoV-2 positive patients, without acute COVID-19, are more likely to have worse brain perfusion after SAH from cerebral aneurysm rupture. [ABSTRACT FROM AUTHOR]

Weekend admission has been reported to be associated with poor clinical outcomes of various diseases. This study aimed to determine whether weekend admission increases the incidence of hospital-acquired pneumonia (HAP) in patients with aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively analyzed aSAH patients admitted to our hospital between 2014 and 2020. These patients were divided into weekend and weekday groups. We compared the incidence of HAP and other clinical outcomes between the two groups. Risk factors for HAP were identified by logistic regression analysis. Of 653 included aSAH patients, 145 (22%) were admitted on weekends and 508 (78%) were admitted on weekdays. The incidence of HAP in the weekend group was significantly higher than that in the weekday group (25% vs 16%, P = 0.01). The weekend group showed worse clinical outcomes, including worse neurological outcome (74% vs 65%, P = 0.03), higher risk of intensive care unit (ICU) admission (21% vs 13%, P = 0.01) and longer length of stay (21.3 vs 16.4 days, P < 0.01). Age ≥ 60 years (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.3–3.0, P < 0.01), modified Fisher score (MFS) ≥ 3 (OR = 1.7, 95% CI = 1.1–2.6, P = 0.02), weekend admission (OR = 1.8, 95% CI = 1.1–2.8, P = 0.02) and operative treatment (OR = 2.3, 95% CI = 1.2–4.5, P = 0.02) were risk factors for HAP following aSAH. Weekend admission was associated with a higher incidence of HAP in aSAH patients. This study suggested that medical administrators may need to optimize healthcare services on weekends. [ABSTRACT FROM AUTHOR]

Multifunctional nature of phytochemicals and their chemical diversity has attracted attention to develop leads originated from nature to fight COVID-19. Pharmacological activities of chelerythrine and its congeners have been studied and reported in the literature. This compound simultaneously has two key therapeutic effects for the treatment of COVID-19, antiviral and anti-inflammatory activities. Chelerythrine can prevent hyper-inflammatory immune response through regulating critical signaling pathways involved in SARS-CoV-2 infection, such as alteration in Nrf2, NF-κB, and p38 MAPK activities. In addition, chelerythrine has a strong protein kinase C-α/-β inhibitory activity suitable for cerebral vasospasm prevention and eryptosis reduction, as well as beneficial effects in suppressing pulmonary inflammation and fibrosis. In terms of antiviral activity, chelerythrine can fight with SARS-CoV-2 through various mechanisms, such as direct-acting mechanism, viral RNA-intercalation, and regulation of host-based antiviral targets. Although chelerythrine is toxic in vitro, the in vivo toxicity is significantly reduced due to its structural conversion to alkanolamine. Its multifunctional action makes chelerythrine a prominent compound for the treatment of COVID-19. Considering precautions related to the toxicity at higher doses, it is expected that this compound is useful in combination with proper antivirals to reduce the severity of COVID-19 symptoms. [ABSTRACT FROM AUTHOR]

Cerebral vasospasm is an important event that occurs following subarachnoid hemorage which has significant mortality and morbidity. The goal in this study was to investigate the effect of pentoxifylline on vasospasm in an experimental subarachnoid hemorrhage model. In this study, 20 male New Zeland White rabbits weighing 3000–3500 g were assigned randomly to four groups. Animals in group 1 served as controls. Animals in group two received only intravenous pentoxifylline injection 3 times in 12 h intervals. In group 3, SAH was induced and no injection was given. Animals in group 4 received intravenous pentoxifylline (6 mg/kg) injections 3 times at 12th, 24th and 36th hours after subarachnoid hemorrhage induction. All animals were sacrificed and basilar arteries were removed at 48th hour. Basilar artery vessel diameters, wall thicknesses and luminal section areas were measured with Spot for Windows version 4.1. Statistical analysis was performed using ANOVA and Kruskall–Wallis tests. Mean basilar artery luminal section areas and luminal diameters in group 4 were significantly higher compared to group 3 (p < 0.05). Basilar artery wall thicknesses and were found to be higher in group 3 than in other groups and this was also statistically significant (p < 0.05). Our study demonstrated that intravenous administration of pentoxifylline significantly decreases vasospasm after subarachnoid hemorrhage. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of herpes simplex encephalitis (HSE) following a successful aneurysm coiling procedure after a subarachnoid hemorrhage (SAH). The patient, a 66-year-old female with a history of chronic obstructive pulmonary disease and liver cirrhosis, presented with expressive dysphasia and right-sided hemiplegia. Despite initial improvement, the patient experienced respiratory failure, confusion, and deteriorating neurology. The diagnosis of HSE was confirmed through positive HSV-2 PCR findings in the cerebrospinal fluid, and treatment with intravenous acyclovir led to resolution of symptoms. This case highlights the importance of considering HSE in neurosurgical patients with unexplained persistent pyrexia and neurological deterioration. [Extracted from the article]

Objective: Early permanent cerebrospinal fluid (CSF) diversion for hydrocephalus during the first 2 weeks after aneurysmal subarachnoid hemorrhage (aSAH) shortens the duration of external ventricular drainage (EVD) and reduces EVD-associated infections (EVDAI). The objective of this study was to detect any association with symptomatic delayed cerebral vasospasm (DCVS), or delayed cerebral ischemia (DCI) by the time of hospital discharge. Methods: We used a single-center dataset of aSAH patients who had received a permanent CSF diversion. We compared an 'early group' in which the procedure was performed up to 14 days after the ictus, to a 'late group' in which it was performed from the 15th day onward. Results: Among 274 consecutive aSAH patients, 39 (14%) had a permanent CSF diversion procedure with a silver-coated EVD. While the blood clot burden was similarly distributed, patients with early permanent CSF diversion (20 out of 39; 51%) had higher levels of consciousness on admission. Early permanent CSF diversion was associated with less colonized catheter, a shorter duration of extracorporeal CSF diversion (OR 0.73, 95%CI 0.58–0.92 per EVD day), and a lower rate of EVDAI (OR 0.08, 95%CI 0.01–0.80). The occurrence of CSF diversion device obstruction, the rate of symptomatic DCVS or detected DCI on computed tomography and the likelihood of a poor outcome at discharge did not differ between the two groups. Discussion: Early permanent CSF diversion lowers the occurrence of catheter colonization and infectious complication without affecting DCVS-related morbidity in good-grade aSAH patients. These findings need confirmation in larger prospective multicenter cohorts. Abbreviations: aSAH: aneurysmal subarachnoid hemorrhage; BNI: Barrow Neurological Institute Scale; CSF: Cerebrospinal fluid; DCVS: Delayed Cerebral Vasospasm; DCI: Delayed Cortical Ischemia; EKNZ: Ethik-Kommission Nordwest Schweiz; EVD: External ventricular drain; EVDAI: External ventricular drain-associated infections; GCS: Glasgow Coma Scale; IRB: Institutional Review Board; IVH: Inraventricular hemorrhage; mRS: Modified Rankin Scale; SOS: Swiss Study of Subarachnoid Hemorrhage Registry; WFNS: World Federation Neurological-Surgeon Scale [ABSTRACT FROM AUTHOR]

The neurological application of long-term electroencephalography (EEG) monitoring in the intensive care unit (ICU) has been implemented in many healthcare institutions. The use of EEG as a monitoring tool in the ICU affords many potential benefits. Uses include the identification of seizures, vasospasm following subarachnoid hemorrhage (SAH), the assessment of coma and the determination of brain death. Neurologic critical care is focused on recognition and treatment of secondary insults. Often treatment is withheld because these insults are not recognized early enough until an irreversible deficit manifest. Continuous EEG (cEEG) monitoring provides a unique potential to recognize these insults and offers an opportunity for early intervention. Why should we continuously monitor the brain with EEG in the ICU? Nonconvulsive seizures (NCS) are common in comatose patients. Nonconvulsive Status Epilepticus (NCSE) and NCS1 are damaging to brain tissue; thus, rapid control of seizures is essential to preserving brain function. With the increased use of cEEG in critical care areas, the purpose of this paper is to examine the use and benefits of EEG monitoring of ICU patients, review the indications for the use of cEEG and discuss technical issues and concerns when performing cEEG monitoring. This article has been divided into six distinct sections: (1) Seizures, NCS, and NCSE (2) Periodic Discharges2 and Patterns on the Ictal-interictal Continuum, (3) Cerebral Ischemia, SAH, and Delayed Cerebral Ischemia (DCI), (4) Encephalopathy and Coma (5) ECI and Brain Death, and (6) ICU-cEEG Monitoring Techniques. [ABSTRACT FROM AUTHOR]

Background/Objective: Stroke is a potentially fatal complication of sickle cell disease (SCD). Transcranial Doppler (TCD) is useful at identifying increased risk of stroke in children with SCD and vasospasm after subarachnoid hemorrhage. The main aim of this study was to determine the proportion of patients with SCD in the Gulf region who are at a high risk of stroke, as determined by TCD. Methods: This multicenter (Oman, Qatar, and UAE), descriptive, cross-sectional study in patients (aged 2–16 years) with SCD included a baseline visit, 1 follow-up visit for patients with conditional TCD, and 3-year retrospective data analysis for all patients. Results: Of the 410 eligible patients (Oman, 86.5%; Qatar, 8.2%; UAE, 5.1%), most had a TCD finding (left side, 91.7%; right side, 92.0%) of normal velocity (<155 cm/s) at baseline. For 6 of 7 patients with conditional velocity (155–179 cm/s) and 1 patient with high velocity (≥180 cm/s), baseline TCD results were not confirmed at follow-up. As per bivariate linear regression, age, race, transfusion type, and transfusion frequency were significant predictors of the TCD velocities. Multivariate logistic regressions revealed that TCD velocities were significantly correlated with sex, race, and type of transfusion. No patients reported any adverse events at follow-up. No deaths occurred during the study. Discussion/Conclusions: The study results show that far fewer patients with SCD in the Gulf have abnormal TCD findings than the internationally reported. Larger studies are needed to identify the factors underlying this observation. [ABSTRACT FROM AUTHOR]

The study aimed to identify key genes involved in cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH). GSE46696 of basilar arteries of SAH mice and normal controls were downloaded from the Gene Expression Omnibus (GEO). Integrated microarray analysis was performed to identify differentially expressed genes (DEGs). GO and KEGG pathway enrichment analyses of DEGs were performed with ClueGO. The protein–protein interaction (PPI) networks were constructed using Cytoscape software. A total of 4103 DEGs were identified; among them, 254 DEGs (63 up-regulated genes and 191 down-regulated genes) showed significant differences at p < 0.05. GO analysis showed that the identified DEGs were over-represented in 16 GO terms. KEGG pathway analysis showed that pathways in immune inflammation were significantly enriched pathways for DEGs. DEGs with relatively frequent interactions after CVS secondary to SAH included MIKI, Cmpk2, TIr3, Psmb9, Ddx58, Lgals9, Ifi44, Stat2, Rsad2, Oas2, Usp18, H28, Irf7 and als3bp. Multiple genes were involved in the regulation of the immune response in the pathogenesis of SAH, including Ripk3, Ifih1, IL10, Reg3g, SIc11a1, NF-κB, Tlr7, Parp9, Rab7b, Dhx58, Gpx2, Zbp1, Aim2, Rsad2, Lgals9, TLR4, Adar, Zc3hav1, KIrk1, Irf7, IL-1β, Trafd1, Ddx58 and Trim5. Our findings revealed the gene expression profiles of the cerebral arteries in SAH mouse models, and speculated that DHx58 gene plays an important role in the immune response through regulating inflammatory cytokines expression, which may be a potential target in the treatment of CVS after SAH. Our finding provided new clues for understanding the mechanism of SAH. [ABSTRACT FROM AUTHOR]

Radiological and clinical cerebral vasospasm (CV) is defined either as a delayed narrowing of cerebral arteries after aneurysmal subarachnoid hemorrhage (aSAH) or/and occurrence of new neurological deficit/worsening of Modified Glasgow coma score for 2 or more points. The objective of this study is to determine the presence and correlation between clinical and radiological presence of vasospasm in patients with aSAH. This study was designed as a clinical, prospective single center study at the Clinic of Neurosurgery, Clinical Center of Vojvodina, Novi Sad, Serbia. A total of 50 patients was included in the study after having radiologically confirmed aSAH. Intensity and region of CV was determined by CT and CTA performed both on admission and on day 9 of hospitalization, except for cases where clinical protocol required earlier imaging due to occurrence of clinical signs and symptoms of CV. In all patients, values of arterial blood pressure (PABP), headache (HA), body temperature (PBT), nonspecific behaviors (NSB), deterioration of consciousness (DC), new neurological deficit (NND), deterioration of two points or more per modified Glasgow Coma Scale (DmGCS ≥ 2) were monitored. CTA showed angiographic vasospasm detected in 100% patients with aSAH. Statistically significant positive correlation was found between the intensity of radiological CV and appearance of NND and DmGCS ≥ 2. This study confirms that CV always follows aSAH. Future research into pathophysiology of CV is needed in order to determine exact treatment strategies and targets so treatment towards zero mortality can be achieved. [ABSTRACT FROM AUTHOR]

Objective: Delayed cerebral ischemia (DCI) and seizures are dreaded neurological complications following aneurysmal subarachnoid hemorrhage (SAH). They may lead to severe mortality or mobility. Continuous electroencephalography (cEEG) is quite useful for secondary brain injury monitoring. This study aims to assess the effectiveness and sensitivity of cEEG in detecting DCI and seizures. Methods: Reports published up to July 31, 2018 were retrieved from PubMed, Medline, Cochrane and EMABSE. A systematic review was carried out on eligible studies. Results: 1. DCI was diagnosed in 20%–62% of aSAH patients, which was detected by a decrease on alpha/delta ratio; DCI can be predictive from 7 h to 1.9 days prior to standard diagnosis by CT, TCD and MRI. 2. Nonconvulsive status epilepticus (NCSE) occurred in 2.9%–30.8% of aSAH patients, and nonconvulsive seizures (NCSZ) in 6–23%; poor outcomes (high disability and mortality) were associated with NCSE. Conclusions: cEEG is an effective monitoring tool for early detection of DCI and seizures, which may help to improve the diagnostic accuracy and provide early treatment for patients with aSAH. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is known as an acute catastrophic neurological disease that continues to be a serious and significant health problem worldwide. The mechanisms contributing to brain injury after SAH remain unclear despite decades of study focusing on early brain injury (EBI) and delayed brain injury (DBI). Neuroinflammation is a well-recognized consequence of SAH and may be responsible for EBI, cerebral vasospasm, and DBI. Toll-like receptors (TLRs) play a crucial role in the inflammatory response by recognizing damage-associated molecular patterns derived from the SAH. TLR4 is the most studied Toll-like receptor and is widely expressed in the central nervous system (CNS). It can be activated by the extravasated blood components in myeloid differentiation primary response-88/Toll/interleukin-1 receptor-domain-containing adapter-inducing interferon-β (MyD88/TRIF)-dependent pathway after SAH. Transcription factors, such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF), that regulate the expression of proinflammatory cytokine genes are initiated by the activation of TLR4, which cause the brain damage after SAH. TLR4 may therefore be a useful therapeutic target for overcoming EBI and DBI in post-SAH neuroinflammation, thereby improving SAH outcome. In the present review, we summarized recent findings from basic and clinical studies of SAH, with a primary focus on the biological characteristics and functions of TLR4 and discussed the mechanisms associated with TLR4 signaling pathway in EBI and DBI following SAH. [ABSTRACT FROM AUTHOR]

Objectives: Cx43 phosphorylation is involved in the pathogenesis of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). However, the exact phosphorylation mechanism of Cx43 in CVS is not fully elucidated. Thus, we examined the role of P38MAPK in CVS and Cx43 phosphorylation, using a double hemorrhage rat model. Methods: Sprague-Dawley rats weighing 300-350 g were grouped into sham, SAH, vehicle, and SAH + SB203580. SAH was induced by double injecting blood into the prechiasmatic cisterns. Neurological score was measured with the Garcia scoring system, and the diameters of basilar arteries and the expression of pCx43, pP38MAPK, and P38MAPK proteins were measured through pressure myograph measurement and Western blot analysis, respectively. Results: The neurological scores remarkably decreased after SAH but remarkably improved after SB203580 was used. The results of pressure myograph analysis on the SAH and vehicle groups showed the considerable narrowing of the basilar arteries in comparison with that of the sham group. By contrast, the arterial diameters in the SAH + SB203580 group were much larger than those observed in the SAH and vehicle groups. Moreover, the P38MAPK expression in the sham group had no substantial change in contrast to the SAH and vehicle groups, and pCx43 and pP38MAPK increased in the SAH and vehicle groups. Meanwhile, the SAH + SB203580 group showed marked decrease in Cx43 and P38MAPK phosphorylation levels relative to the SAH and vehicle groups. Conclusions: P38MAPK pathway facilitates the development of CVS through the upregulation of Cx43 phosphorylation. [ABSTRACT FROM AUTHOR]

Introduction: Despite advancements in medical and surgical therapies, clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH) continue to be poor. Currently, aSAH pathophysiology remains poorly understood. No aSAH biomarkers are commonly used in the clinical setting. This exploratory study used metabolomics profiling to identify global metabolic changes and metabolite predictors of long-term outcome using cerebrospinal fluid (CSF) samples of aSAH patients. Methods and methods: Gas chromatography time-of-flight mass spectrometry was applied to CSF samples collected from 15 consecutive high-grade aSAH patients (modified Fisher grade 3 or 4). Collected CSF samples were analyzed at two time points (admission and the anticipated vasospasm timeframe). Metabolite levels at both time points were compared and correlated with vasospasm status and Glasgow Outcome Scale (GOS) of patients at 1 year post-aSAH. Significance level was defined as p < 0.05 with false discovery rate correction for multiple comparisons. Results: Of 97 metabolites identified, 16 metabolites, primarily free amino acids, significantly changed between the two time points. These changes were magnified in modified Fisher grade 4 compared with grade 3. Six metabolites (2-hydroxyglutarate, tryptophan, glycine, proline, isoleucine, and alanine) correlated with GOS at 1 year post-aSAH independent of vasospasm status. When predicting patients who had low disability (GOS 5 vs. GOS ≤4), 2-hydroxyglutarate had a sensitivity and specificity of 0.89 and 0.83 respectively. Conclusions: Our preliminary study suggests that specific metabolite changes occur in the brain during the course of aSAH and that quantification of specific CSF metabolites may be used to predict long-term outcome in patients with aSAH. This is the first study to implicate 2-hydroxyglutarate, a known marker of tissue hypoxia, in aSAH pathogenesis. [ABSTRACT FROM AUTHOR]

As mobile imaging and application technology develops at a rapid pace, new products with potential value to healthcare emerge. This paper explores the usefulness of mobile thermal imaging technology in the documentation of Raynaud’s phenomenon. Using a single-case study, a patient’s symptoms were recorded using a FLIR ONE® PRO for one month along with data relating to temperatures and weather conditions, diet and exercise and anxiety levels. Pearson Correlation Coefficient tests were carried out to determine if symptom onset could be better understood. [ABSTRACT FROM AUTHOR]

Purpose: Arterial vasospasm is a major cause of death and long-term disability following subarachnoid haemorrhage (SAH). The use of medically induced hypertension, hypervolaemia and/or haemodilution is widely practiced for prophylaxis and treatment of vasospasm following SAH. We aimed to determine if the quality of available research is adequate to inform use of haemodynamic management strategies to prevent or treat vasospasm following SAH. Methods: Individual searches of the following databases were conducted: The Cochrane Database of Systematic Reviews, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and OpenSIGLE. Pertinent randomised clinical trials and cohort studies comparing any element or combination thereof: medically induced hypertension, hypervolaemia, and haemodilution were included. Data were extracted using standardised proformas and risk of bias assessed using a domain-based risk of bias assessment tool. Results: 348 study reports were identified by our literature search. Eight studies were included, three of which examined both volume expansion and medically induced hypertension. Three randomised clinical trials and two cohort studies examining prophylactic volume expansion were included. Two trials of prophylactic medically induced hypertension and two cohort studies were included. One trial and one cohort study of medically induced hypertension for treatment of established vasospasm was included. These trials demonstrated no significant difference in any of the clinical outcome measures studied. No trials of blood transfusion were included. Conclusions: There is currently insufficient evidence to determine the efficacy or non-efficacy of intravenous volume expansion, medically induced hypertension or blood transfusion for the treatment or prophylaxis of vasospasm following SAH. All of these approaches have been associated with adverse events, of unclear incidence. The current evidence base therefore cannot be used to reliably inform clinical practice. This is a priority for further research. [ABSTRACT FROM AUTHOR]

Objective: Cerebral vasospasm(CVS) after Subarachnoid hemorrhage (SAH) can cause delayed cerebral ischemia,secondary cerebral infarction, and rehemorrhage, which are the leading causes of mutilation and death. Nimodipine has been shown to prevent CVS. Magnesium ion (Mg2+) can competitively inhibit the influx of calcium (Ca2+) and prevent vasospasm. There is evidence that magnesium sulfate can prevent CVS and reduce infarct volume after SAH. In this study, we evaluated the efficacy and safety of intravenous magnesium sulfate combined with oral nimodipine on CVS, delayed cerebral ischemia, secondary cerebral infarction, and rehemorrhage after SAH. Methods: This is a prospective randomized, double-blind trial of 120 patients with SAH who were recruited between January 2003 and January 2009. These patients were assigned to two groups and received the same basic treatment and symptomatic treatment. In group A, patients received 14 days of intravenous administration of 1400 mL 0.9% normal saline + 40 mL 25% magnesium sulfate, 1 mL/min, once per day, followed 7 days of intravenous administration of 500 mL 0.9% normal saline + 15 mL 25% magnesium sulfate, 1 mL/min, once per day and oral nimodipine, 20 mg once, four times a day, for 21 days. Patients in group B received identical treatment to that in group A, except that 25% magnesium sulfate was replaced by placebo. On day 22 of treatment, incidences of intracranial CVS, delayed cerebral ischemia, secondary cerebral infarction, rehemorrhage, neurologic deficits, and death were assessed and adverse events were monitored. Results: CVS occurred in 4, 12 patients, lasting for 11.09 ± 5.38, 13.73 ± 6.24 hours, mean velocity (Vm) of 143.2 ± 12.7, 149.6 ± 18.9 cm/s in group A, B; Delayed cerebral ischemia occurred in 3, 10 patients, lasting for 13.16 ± 4.82, 15.57 ± 5.35 hours in group A, B; Secondary cerebral infarction occurred in 2 and 8 patients in groups A and B; Neurologic deficits occurred in3 and 11 patients in groups A and B, All P < 0.05; Rehemorrhage occurred in 4 and 5 patients; Death occurred in 5 and 8 patients in groups A and B, respectively, P >0.05. No obvious adverse events were found in both groups. Conclusion: Intravenous magnesium sulfate in combination with oral nimodipine for the treatment of SAH can help reduce the incidences of CVS, delayed cerebral ischemia, secondary cerebral infarction, and neurologic deficits with good safety, but it does not reduce the incidences of rehemorrhage and death. [ABSTRACT FROM AUTHOR]

Free radical toxicity is considered as a key mechanism in the neuronal damage occurring after aneurysmal subarachnoid haemorrhage (SAH). We measured markers of DNA and RNA damage from oxidation (8-oxodG and 8-oxoGuo, respectively) in cerebrospinal fluid from 45 patients with SAH on day 1–14 after ictus and 45 age-matched healthy control subjects. At baseline, both markers were significantly increased in patients compared to controls (pvalues < .001), and exhibited a progressive further increase (to >20-fold above control levels) from day 5–14. None of the markers predicted the occurrence of vasospasms or mortality, although there was a trend that the 8-oxoGuo marker was more strongly associated with mortality than the 8-oxodG marker. We conclude that SAH leads to a massive increase in damage to nucleic acids from oxidative stress, which is likely to play a role in neuronal dysfunction and death. As only patients in need of a ventriculostomy catheter were included in the study, the findings cannot necessarily be extrapolated to all patients with SAH. [ABSTRACT FROM PUBLISHER]

Background:Reversible cerebral vasoconstriction syndrome (RCVS), also known as Call-Fleming syndrome, is characterized by thunderclap headaches, non-aneurysmal segmental cerebral vasoconstriction seen on arteriogram, and spontaneously resolves within 12 weeks. Fingolimod has been reported to cause posterior reversible encephalopathy syndrome (PRES) and one case of RCVS.Objective:We report a case of RCVS possibly related to fingolimod use, and compare to cases of adverse outcomes in fingolimod use.Methods:This is a single observational study without controls; therefore, level of evidence is IV. A literature review in pubmed with keywords, fingolimod, vasospasm, RCVS, Call-Fleming, stroke, PRES and hemorrhage.Results:One case of RCVS on fingolimod in the post-partum period. Two other cases in the literature were found one with hemorrhagic encephalitis and the other critical vasospasm in the upper extremity associated with fingolimod 1.25 mg daily in the FREEDOMS II trial and TRANSFORMS study, respectively. Additionally, Novartis reports nine cases of PRES related to fingolimod use.Conclusion:Fingolimod has the potential to cause vasoconstriction however appears to be rare and more likely on doses higher than 0.5 mg daily. Fingolimod may be associated in RCVS and should be considered in patients with severe headache on fingolimod. [ABSTRACT FROM PUBLISHER]

Objective:Evidence suggests that reduction of nitric oxide (NO) bioavailability due to oxidative stress plays a central role in the pathophysiology of cerebral vasospasm after subarachnoid haemorrhage (SAH). To prevent SAH-induced cerebral vasospasm, therefore we used nebivolol hydrochloride as a NO–mediated vasodilator and an antioxidant drug in an experimental rat model of SAH. Materials and methods:Forty female Wistar rats were divided into control, SAH, SAH plus placebo, and SAH plus nebivolol groups. Starting six hours after inducing SAH, 5 mg/kg of nebivolol hydrochloride and of pharmaceutical excipients of nebivolol was given orally once daily for five days to SAH plus nebivolol and SAH plus placebo groups, respectively. The lumen diameter and vessel wall thickness of the basilar artery were measured in brain sections. The serum and brain supernatant levels of nitric oxide (NO) were analysed. The brain supernatant levels of intrinsic antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as markers of the antioxidant status. Results:Nebivolol administration attenuated cerebral vasospasm both by increasing NO levels and by decreasing oxidative stress. Our study also demonstrated that nebivolol administration reverses SAH created imbalance between SOD and GSH-Px by increasing GSH-Px activity relative to SOD. Conclusions:Nebivolol attenuates the cerebral vasospasm after SAH both increasing NO levels and decreasing oxidative stress. Therefore, it may promise to prevent SAH-induced cerebral vasospasm as an anti-spasmodic and anti-oxidant agent. [ABSTRACT FROM PUBLISHER]

This study aimed to investigate the therapeutic effect of glycyrrhizic acid (GA) on the cerebral vasospasm (CVS) in a rat subarachnoid hemorrhage (SAH) model and to explore the potential mechanism. A total of 44 healthy male rats were randomly assigned into 3 groups: control group (n = 12), SAH group (n = 16) and GA group (n = 16). No treatment was conducted in control group; in SAH group and GA group, experimental CVS was induced using a double-hemorrhage model and then rats were intraperitoneally injected with normal saline and GA at 10 mg/kg, respectively, once daily. Three days later, neurological function was evaluated. Then, animals were sacrificed, and the basilar artery was collected. The inner diameter and vascular wall thickness were determined. Western blotting was employed to detect high mobility group protein B1 (HMGB1) protein expression and RT-PCR to detect the mRNA expression of IL-1β, IL-6, TNF-α, and IL-10 in the basilar artery. GA treatment significantly improved the neurological function following SAH. In GA group, the basilar artery diameter increased markedly and vascular wall thickness reduced significantly when compared with SAH group (p < 0.05). HMGB1 protein expression and mRNA expression of IL-1β, IL-6, TNF-α, and IL-10 in SAH group were significantly higher than in control group (p < 0.05). However, GA dramatically reduced IL-1β, IL-6, and TNF-α, and further elevated IL-10 expression as compared to SAH group (p < 0.05). GA may inhibit HMGB1 expression and subsequent production of inflammatory cytokines to prevent CVS following SAH. [ABSTRACT FROM PUBLISHER]

An 18-year-old patient developed multiple infarcts, nine days after endoscopic fenestration of a large arachnoid cyst. We consider vasospasm to be the most likely cause, presumably triggered by a chemical meningitis. Although mostly seen after subarachnoid haemorrhage, vasospasm can also occur after traumatic brain injury, brain surgery or meningitis. [ABSTRACT FROM AUTHOR]

Unlike other aneurysmal SAH patients with a favorable neurological course, the patient needed oxygen therapy for the first week. This case shows a ruptured intracranial aneurysm Hunt and Hess grade 1, Fisher 2, tested Covid-19 positive, with two subsequent negative tests and a favorable clinical course. To the Editor, During the pandemic, we continued to treat Covid-19 positive neurosurgical patients.[1] Occasionally patients with neurovascular hemorrhage have tested SARS-CoV-2 positive. [Extracted from the article]

Introduction:Balloon angioplasty and/or selective intra-arterial vasodilator therapies are treatment options in patients with vasospasm after subarachnoid hemorrhage (SAH). We analyzed the effect of balloon angioplasty and/or selective intra-arterial vasodilator therapy in our patients. Methods:Twenty-six patients (vasodilation group, VDT) were treated with intra-arterial nimodipine. The balloon angioplasty with nimodiopine-group (BAP-N group) comprised 21 patients. The primary endpoint of this study was successful angiographic vessel dilation in vasospastic vessels after balloon angioplasty, together with nimodipine (BAP-N group), compared to intra-arterial vasodilator therapy (VDT group) with nimodipine alone. Results:A significant effect of angioplasty plus nimodipine was found in the central arteries (composite endpoint) with an OR of 2.4 (95% CI: 1.4–4.2],p = 0.002), indicating a chance of improvement of the BAP-N group of more than twice compared to nimodipine infusions alone. Significant advantages for BAP-N-therapy were also encountered in the internal carotid artery (OR 5.4,p < 0.001) and basilar artery (OR 29.7,p = 0.003). A joint analysis of all arteries combined failed to show significant benefit of BAP-N therapy (OR 1.5,p = 0.079), which was also true for cerebral peripheral arteries (OR 0.77,p = 0.367). There was no difference in clinical outcome between both groups. Conclusions:In SAH patients with vasospasm, a combination therapy of balloon angioplasty and intra-arterial nimodipine resulted in a more than doubled vasodilative effect in the central cerebral arteries compared to the sole infusion of nimodipine. Regarding the ICA and BA arteries, this beneficial effect was even more pronounced. Although there was a tendency of better effects of the BAP-N group, regarding the overall effect in all territories combined, this failed to reach statistical evidence. In cerebral peripheral arteries, no differences were observed, and there was no difference in clinical outcome, too. [ABSTRACT FROM AUTHOR]

Object/Background: Vasospasm is a common cause of mortality and morbidity following rupture of intracranial aneurysm. Hemodynamic therapy instituted in these patients in the past has been replaced by direct manipulation of the spastic vessels by angioplasty and intra-arterial infusion of vasodilators. However, no case control studies exist proving its superiority. The purpose of our study was to compare the efficacy of intra-arterial nimodipine (IAN) to that of hemodynamic therapy in patients with vasospasm following aSAH.Material and methods: Fifty-three patients who developed vasospasm following aSAH were included in the study. IAN was instilled in addition to hemodynamic therapy in 39 patients and 14 patients (who refused to give consent for IAN) were continued on hemodynamic therapy alone and served as controls. The response to IAN was studied on angiogram. The clinical response was assessed in both the groups at regular intervals. IAN was repeated if necessary. The outcome (GOS) at discharge and at 3 months after discharge was compared.Results: Thirty-six (92.3%) out of 39 patients showed immediate angiographic reversal of vasospasm.28 of them showed clinical response, of which only 11 had lasting response. 11(28.2%) of 39 patients who received IAN had a good outcome at discharge and 23(58.9%) had a favourable outcome at 3 months follow up. In those who received hemodynamic therapy alone, 4 out of 14(28.6%) patients had a good outcome at discharge and 8 (57.1%) a favourable outcome at 3 months.Conclusions: Angiographic reversal of vasospasm is seen in majority of the patients following IAN. However, this does not necessarily translate into a long lasting clinical response. The final outcome in patients who received hemodynamic therapy is comparable to those who received additional IAN. IAN does not appear to provide a major added advantage over the conventional hemodynamic therapy. [ABSTRACT FROM AUTHOR]

Objectives: Growing evidence suggests that oxidative stress is one of the factors contributing to subarachnoid haemorrhage (SAH)-induced cerebral vasospasm. SAH-induced cerebral vasospam alters thioredoxin (Trx) cycle enzymes and thioredoxin-interacting protein (TXNIP) as an important endogenous antioxidant system. In this study, we have explored the effects of telmisartan on the vascular morphological changes, endothelial apoptosis, tissue oxidative stress status and the level of Trx cycle enzymes/ TXNIP in a rabbit SAH model. Methods: Forty male New Zealand rabbits were randomly divided into five groups of eight rabbits each: control group, sham group, SAH group, SAH + vehicle group and SAH + telmisartan group. SAH was created by a single cisterna magna blood injection. SAH + telmisartan group received telmisartan treatment (5 mg/kg intraperitoneal, once daily) for 72 h. The brainstem tissue Trx1, Trx2, Trx reductase (TrxR), TrxR1and TXNIP levels were investigated. Total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA) levels and tumour necrosis factor alpha (TNF alpha) levels were investigated. Basilar artery segments were investigated for cross-sectional area, wall thickness measurements and endothelial apoptosis. Results: Telmisartan treatment restored the lowered level of Trx1, TrxR, TAS and the expression of TrxR1 seen in SAH. Telmisartan treatment also decreased TXNIP expression, TOS, MDA and TNF alpha levels. Morphological changes of cerebral vasospasm were attenuated after treatment. Endothelial apoptosis significantly reduced. Discussion: Treatment with telmisartan ameliorates oxidative stress and SAH-induced cerebral vasospasm in rabbits. These effects of telmisartan may be associated with downregulation of TXNIP and upregulation of Trx/TrxR. [ABSTRACT FROM AUTHOR]

Objectives: Cerebral vasospasm (CVS) and early brain injury are major causes of morbidity and mortality following subarachnoid hemorrhage (SAH). We investigated the efficiency of human tissue kallikrein (HTK) to prevent CVS in a rabbit model of SAH. Methods: Forty-eight Japanese white rabbits were randomly divided into four groups (n = 12 each): control (sham-operated), SAH, SAH + phosphate-buffered saline (PBS, vehicle), and SAH + HTK. Basilar artery (BA) diameters were measured by three-dimensional computed tomography angiography at three time points. Endothelin-1 (ET-1) and nitric oxide (NO) levels in the cerebrospinal fluid (CSF) were assayed 24 h before and 5 and 7 days after SAH. After the last measurement, the animals were killed, and endothelial cell apoptosis was assessed. Bax and Bcl-2 levels in the BA were measured by western blotting. Results: HTK was found to significantly reduce CVS following SAH in rabbits. Inverse changes were observed in ET-1 and NO levels in the CSF collected from the SAH group. HTK increased levels of NO, which has a vasodilatory effect, but did not affect levels of ET-1, which has a vasoconstrictive effect. CTA revealed that HTK treatment significantly increased BA diameter. Moreover, HTK treatment reduced the number of apoptotic cells following SAH, presumably by increasing and decreasing Bcl-2 and Bax expression, respectively. Conclusion: HTK ameliorated CVS and inhibited apoptosis in the BA in a rabbit model of SAH. [ABSTRACT FROM AUTHOR]

Objectives: It has been suggested that metalloproteinase-9 (MMP-9) could predict the onset of cerebral vasospasm after subarachnoidal haemorrhage (SAH). The aim of this study was to analyse, in patients with SAH, the difference between patients with MRI ischaemic infarcts and patients without, and to investigate the role of metalloproteases as a prognostic factor for ischaemic infarcts. Methods: Sixty eight consecutive patients with SAH and diffusion-weighted magnetic resonance imaging (DWI-MRI) done 3 weeks after SAH. We define two groups, with and without DWI-MRI infarcts. Blood samples were taken at entry, 3 days and 1 week MMP-9 was determined through ELISA method. Results: Forty per cent were male, with a mean age of 54± 14 years. Twenty five patients, 36.8%, had DWIMRI infarcts; in patients with MRI infarcts, SAH was more severe (Fisher=4 52 vs 25.6%, P=0.037), with more morbi-mortality (Rankin>3 48 vs 18.6%, P=0.014), and more symptomatic vasospasm (28 vs 7%, P=.031). Levels of MMP-9 were higher than controls, but there were no significant differences between patients with and without infarcts (first determination no infarcts 39.40 ng/ml± 35.40 vs infarcts 49.75 ng/ml± 34.54, P>0.005, 3 days no infarcts 72.10 ng/ml± 70.95 vs infarcts 62.28± 33.84, P>0.005, 1 week no infarcts 148.48 ng/ml± 142.73 vs infarcts 91.51 ng/ml± 41.20, P>0.005). Conclusion: Thirty eight percent in a well-studied series of patients with SAH have DWI-MRI infarcts; the infarcts were associated to SAH severity, SAH outcome and symptomatic vasospasm. Metalloproteinase- 9 was higher in SAH patients than in controls, but it could not discriminate the infarct patients. [ABSTRACT FROM AUTHOR]

Objectives: Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is characterized by the severe constriction of an artery, which often leads to unfavorable outcomes. CVS after SAH is closely associated with asymmetric dimethylarginine (ADMA) and connexin. The effect of 18β-glycyrrhetinic acid (18β-GA), an inhibitor of gap junction, on ADMA, connexin, and CVS after SAH were investigated. Methods: Sprague-Dawley rats (n = 120), weighing 300-350 g, were divided into the control group, sham, SAH, and SAH + 18β-GA groups. In the SAH group, blood was injected into the prechiasmatic cistern of the rats, and 18β-GA (10 mg/kg) was intraperitoneally injected. The neurological score, basilar artery diameter, ADMA, and connexin protein contents (Cx40, Cx43, and Cx45) were measured using Kaoutzanis scoring system, pressure myograph, enzyme linked immunosorbent assay kit, and Western blot, respectively, 1, 3, 5, 7, and 14 days after SAH. Results: The neurological score significantly decreased 3, 5, 7, and 14 days after SAH. The basilar artery diameter significantly decreased, and the ADMA level in the cerebrospinal fluid (CSF) significantly increased at all time points. The level of Cx40 significantly decreased on days 3, 5, 7, and 14, and the level of Cx43 and Cx45 significantly increased at all time points. ADMA and Cx43 are positively correlated. However, the upregulated level of ADMA, Cx43, and Cx45 were attenuated. The neurology result significantly improved in the SAH + 18β-GA group. Conclusions: Treatment with 18β-GA in SAH rats decreases Cx43 and Cx45 in basilar artery and ADMA in CSF. ADMA is probably involved in the pathophysiological events of CVS after SAH by altering connexin proteins. The mechanism of connexin protein changes caused by ADMA needs to be further studied. [ABSTRACT FROM AUTHOR]

Objective. Mouse subarachnoid hemorrhage (SAH) models are becoming increasingly important. We aimed to report and discuss the detailed technical-surgical approach and difficulties associated with the circle of Willis perforation (cWp) model, with reference to the existing literature. Methods. First, the cWp model was reproduced using ddY mice following scarification at 0 h, Days 1, 2, and 3 after SAH. Second, C57BL/6 mice were subjected to SAH with histological examination on Days 1, 2, and 3. Sham-operated mice were sacrificed on Day 2. Neurological performance, amount of subarachnoid blood, cerebral vasospasm (CVS), and neuronal injury were assessed. Relevant articles found in the MEDLINE database were reviewed. Results. Induction of SAH was successfully reproduced. The volume of subarachnoid blood decreased with time due to resorption. Neurological performance was worse in SAH compared with sham. Signs of CVS could be confirmed on Days 2 and 3, but not Day 1. The cumulative number of microthrombi was significantly higher on Days 2 and 3, but not Day 1. Apoptotic and degenerative neurons were found in the cortex and hippocampal area. Our review of the literature revealed the cWp model to be the most frequently used. The present findings largely confirmed previously published results. However, detailed technical-surgical description and its discussion were sparse, which we provide here. Conclusions. The current study provides additional useful information characterizing the cWp model. This model may be of first choice at present, as important pathologies can be reproduced and most findings in the literature are based on it. [ABSTRACT FROM AUTHOR]

This study was undertaken to investigate the preventive or therapeutic effect of hyperbaric oxygen therapy (HBOT) on cerebral vasospasm following experimental subarachnoid hemorrhage (SAH). Twenty rabbits were assigned randomly to one of four groups. Animals in Group I were not subjected to SAH or sham operation (control group, n = 5). Animals in Group II were subjected to sham operation and received no treatment after the procedure (sham group, n = 5). Animals in Group III were subjected to SAH and received no treatment after SAH induction (SAH group, n = 5). Animals in Group IV were subjected to SAH and received five sessions of HBOT at 2.4 atmospheres absolute (ATA) for 2 h (treatment group, n = 5). Animals were euthanized by perfusion and fixation 72 h after procedures. Basilar artery vasospasm indices, arterial wall thicknesses, and cross-sectional luminal areas were evaluated. Statistical comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests. Mean basilar artery vasospasm index in the treatment group was significantly smaller than in the SAH group. Mean basilar artery wall thickness in the treatment group was significantly smaller than in the SAH group. Mean basilar artery cross-sectional luminal area in the treatment group showed an increase relative to the SAH group, but this difference remained statistically insignificant. Our results demonstrated that repeated application of HBOT at 2.4 ATA for 2 h attenuated vasospastic changes such as increased vasospasm index and arterial wall thickness. HBOT is thus a promising candidate for SAH-induced vasospasm. Further studies are needed to evaluate maximal effect and optimal application regimen. [ABSTRACT FROM AUTHOR]

Context: Subarachnoid hemorrhage (SAH) has a high fatality rate and many suffer from delayed neurological deficits. Biomarkers may aid in the identification of high-risk patients, guide treatment/management and improve outcome. Objective: The aim of this review was to summarize biomarkers of SAH associated with outcome. Methods: An electronic database query was completed, including an additional review of reference lists to include all potential human studies. Results: A total of 298 articles were identified; 112 were reviewed; 55 studies were included. Conclusion: This review details biomarkers of SAH that correlate with outcome. It provides the basis for research investigating their possible translation into the management of SAH patients. [ABSTRACT FROM AUTHOR]

Objectives: In the human brain, the potent vasoconstrictive neuropeptide Y (NPY) is abundantly expressed. Neuropeptide Y, which is stored in perivascular nerve fibers of the cerebral arteries, regulates the cerebral vascular diameter as well as cerebral blood flow. However, the role of NPY in the pathogenesis of cerebral vasospasm (CV) related to subarachnoid hemorrhage (SAH) is unclear. We prospectively analyzed and compared the release of endogenous NPY in the cerebrospinal fluid (CSF) of 66 patients with SAH to NPY release in a control group. Additionally, we correlated the levels of NPY with CV and consecutive ischemic stroke. Methods: Sixty-six consecutive patients (40 women, 26 men; mean age 53.1 years) with aneurysmal SAH were included. In the SAH group, CSF was drawn daily from day 1 to day 10 after the onset of SAH. The CSF of 29 patients undergoing spinal anesthesia for orthopedic surgery served as control samples. The NPY levels were determined in duplicate CSF samples by means of a competitive enzyme immunoassay (El A). The levels of NPY in CSF were correlated with the development of CV over the 10-day period after the onset of SAH and to the occurrence of consecutive ischemic stroke. To evaluate CSF NPY levels as a predictive biomarker for vasospasm, we calculated the sensitivity and specificity as well as the positive and negative predictive values. Results: The NPY levels were significantly higher in the SAH group than in the control group (p < 0.001). The treatment modality (clip versus coil) did not influence the level of NPY in CSF (p > 0.05). Patients with CV showed significantly higher NPY levels than patients without CV during the entire observation period. The NPY levels of the non-CV group dissipated over time, whereas the CV group showed continuously increasing values. The NPY levels from day 4 to 10 were significantly higher in patients with CV-related stroke than in non-stroke patients. Using 0.3 ng/ml as a cut-off value, NPY levels on day 3 predicted the occurrence of CV with a sensitivity and specificity of 82% and 72%, respectively. High NPY levels, starting on day 4, significantly correlated with poor Glasgow Outcome Score grading at the follow-up (p < 0.05). Discussion: Our data indicate that NPY is involved in the pathogenesis of SAH-related CV and ischemia. Neuropeptide Y represents an early and reliable biomarker for the prediction of CV and consecutive stroke due to aneurysmal SAH. [ABSTRACT FROM AUTHOR]

Nowadays, the scientific community has accepted with very little controversy that oxidative stress plays a key role in the onset and development of human diseases. Oxidative stress is defined as an imbalance between the oxidation of molecules constituting cellular organelles and the antioxidant defenses that the organism has to defend itself against oxidation. Oxidation is associated with inflammation, anti-inflammatory pathways are related to decreased oxidation, increased oxidative stress triggers inflammation, and improvement in redox balance inhibits the inflammatory cellular response [[1]]. [Extracted from the article]

Objectives: Given that reliable markers for early ischemic brain damage are lacking, we set out to test whether pimonidazole can be used as a reliable tool in the quantification of hypoxic insults, at early time points following experimental stroke. Methods: We have used semi-quantitative Western blotting detection of pimonidazole adducts in a rat model of reversible middle cerebral artery occlusion (MCAO), treated with remote post-conditioning. Results: First, we demonstrated that a linear relationship exist between pimonidazole binding in the ischemic hemisphere and duration of ischemia, in animals subjected to 5, 15, 30, or 60 minutes of occlusion followed by 120 minutes of reflow. Then we showed a significant reduction in pimonidazole binding in the infarcted hemisphere, when rats with 60 minutes of MCAO, immediately after establishment of cerebral reflow, had 3×15 minutes intermittent hind limb ischemia followed by 24-hour survival. We analysed the middle cerebral arteries from animals with 60 minutes of MCAO and early remote postconditioning, followed by 30 minutes, 24, or 48 hours of reflow. At 24 hours of reflow increases in phosphorylated protein kinase C-alpha with concomitantly increased levels of p38 phosphorylation were observed. Conclusions: Our investigation demonstrates that pimonidazole can be used for quantifying ischemic impact in stroke, even after very short survival times. It furthermore shows that early remote postconditioning reduces ischemic damage, probably through hyperpolarization and reduced reflow vasospasm in the conduit middle cerebral arteries. [ABSTRACT FROM AUTHOR]